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Mechanism of Immune Response During Immunotherapy
Monica C. Panelli,Dirk Nagorsen,Ena Wang,Vladia Monsurro,Ping Jin,Zavaglia Katia,Kina Smith,Yvonne Ngalame,Francesco M Marincola 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.SUP
Tumor immunology embraces an extensive array of biological phenomena that include interactions between neoplastic cells and the innate and adaptive immune response. Among immune cells, T cells have taken the center stage because they can be easily demonstrated to specifically recognize autologous cancer cells. However, their role is limited and other components of the immune response are likely necessary for the completion of cancer rejection. Metastatic melanoma and renal cell carcinoma (RCC) are malignancies strongly predisposed to regress in response to the systemic administration of high-dose interleukin (IL)-2. Several clinical Studies in extensive cohorts of patients have shown that this treatment can induce complete or partial clinical regressions of metastatic disease in 15 to 20% of patients who receive this treatment.1-6 Although IL-2 has direct pluri-potent effects on cells with immune and inflammatory function, it remains unexplained which cell subset is implicated in mediating tumor regression. In a quest to characterize the mechanism of action of IL-2 during the course of immunotherapy, we have investigated the early changes in transcriptional profiles of circulating mononuclear cells and microenvironment of melanoma metastases following high dose IL-2 administration (720,000IU/kg) by serial sampling of blood cells and tumors in the form of fine needle aspirate (FNA).7 Furthermore, studies are currently ongoing to characterize the proteomic profiling of RCC patients undergoing the same treatment using protein arrays (manuscript in preparation). The predominant activation of genes related to inflammation and activation of mononuclear phagocytes lead us to further characterize this cell subset in the context of stimulation with a panel of soluble factors potentially present in the circulation and tumor microenvironment.
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Quality assessment of cellular therapies: the emerging role of molecular assays
David F. Stroncek,Jiaqiang Ren,Ji Feng,Luciano Castiello,Sara Civini,Ena Wang,Francesco M. Marincola,Marianna Sabatino,Ping Jin 대한혈액학회 2010 Blood Research Vol.45 No.1
Cellular therapies are becoming increasingly important in treating cancer, hematologic malignancies, autoimmune disorders, and damaged tissue. These therapies are becoming more effective and are being used more frequently, but they are also becoming more complex. As a result, quality testing is becoming an increasingly important part of cellular therapy. Cellular therapies should be tested at several points during their production. The starting material, intermediate products and the final product are usually analyzed. Products are evaluated at critical steps in the manufacturing process and at the end of production prior to the release of the product for clinical use. In addition, the donor of the starting biologic material is usually evaluated. The testing of cellular therapies for stability, consistency, comparability and potency is especially challenging. We and others have found that global gene and microRNA expression analysis is useful for comparability testing and will likely be useful for potency, stability and consistency testing. Several examples of the use of gene expression analysis for assessing cellular therapies are presented.
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